Discussion

In this review, a summary of the evidence of topical analgesic and local anaesthetic agents has been provided. Two previous reviews suggest that topical analgesic and topical local anaesthetic agents may be useful in reducing wound-related pain associated with chronic leg ulcers (Briggs et al., 2012; Vanscheidt et al., 2001). Their findings indicated that topical ibuprofen permeated foam was

affective for the same wound type. In both reviews, all studies investigating EMLA® found it to be successful in reducing acute operative pain associated with the debridement of chronic leg ulcers.

This review reported in this thesis on past evidence relating to topical analgesic and local anaesthetic agents as pain management strategies for chronic leg ulcers. Using a systematic approach this present review identified a further six studies that met the inclusion criteria related to EMLA® that were not included in the formative systematic review by Briggs et al. (2012). Only one study was published after 2012. Additionally, a further five studies relating to topical

ibuprofen foam and three studies relating to topical morphine gel were also identified; none were published after 2012. No other studies relating to other topical analgesic or topical local

anaesthetic agents that met our inclusion criteria were found. Findings in this review are similar to previous reviews in that ibuprofen foam and morphine gel were applied as primary dressings to treat chronic wound-related pain. The findings also suggest that ibuprofen foam may be successful in reducing chronic leg ulcer pain, however, there was insufficient data to suggest similar

effectiveness for the application of morphine gel. EMLA® was the local anaesthetic agent used in all studies in the topical anaesthetic group and was applied to chronic leg ulcers to prevent acute pain associated with debridement. The findings from all studies suggested that EMLA® was effective when used for this purpose.

It is important to consider where research on this subject has come from, whether it is robust then build on this previous research (Shorten, 2013). In this review 18 out of 22 studies were RCTs. The purpose of randomisation is to achieve baseline equivalence between study groups so that any change in outcomes can be attributed to the intervention rather than the difference being

potentially explained by differences in group characteristics (Elkins, 2015). The majority of studies in this review did not conform to reporting requirements (Schulz et al., 2010) therefore, the risk of selection, detection and performance biases was often unable to be determined. However, the insufficient information provided in the articles leads to the assumption of poor trial quality but this cannot truly be assessed (Soares et al., 2004). Nevertheless, only 20% of RCTs blinded the participants and investigators, 8% reported how their allocation sequence was generated and only a quarter reported allocation concealment. The risk of attrition bias was also high with less than 20% of RCTs reporting whether participants were accommodated in an ITT analysis and less than 10% reported participant withdrawals. One study in this group had a dropout rate of 29%.

Furthermore, most studies included in this review were older than 5 years, although it is recognised that only valuing recent evidence over robust evidence may misinform practice (Shorten, 2013).

To improve the validity of a clinical trial an appropriate sample size is important to be able to detect a difference between two or more groups as near to reality as possible. A small sample size increases the potential for Type II error resulting in the applicability and utility in the clinical setting unlikely (G. S. Kumar, 2014). Conversely, clinical trials with larger sample sizes can result in a waste of resources decreasing the validity or accuracy of the trial due to a low response-rate and difficulty maintaining data quality (Kumar, 2014). In this review, 13 of the 22 studies had a sample size of less than 100; all studies investigating morphine gel group had sample sizes less than 25 as did two out of seven studies investigating ibuprofen foam and eight out of the 12 investigating EMLA®. Even though the retrospective, observational medical record review had a

very large sample size, the study design has other inherent methodological limitations that sample size alone could not overcome.

In this review, the findings from the evidence relating to topical analgesic and topical local anaesthetic agents for the relief of chronic leg ulcer pain indicates that topical agents are effective in reducing pain associated with chronic leg ulcers except for morphine gel. What this review has added to the body of knowledge is that, to date, the only topical formulations used as primary dressings for chronic leg ulcer pain have been ibuprofen foam and morphine gel. EMLA® has never been used in this novel way even though it is the predominant and most long-standing topical pain-relieving agent used for relief of operative pain associated with the debridement of chronic leg ulcers.

The evidence presented in this review regarding EMLA® supports why it was chosen as the intervention for the study conducted and presented in this thesis. The evidence suggests that EMLA® is a superior topical agent for reducing operative pain associated with the debridement of chronic leg ulcers, is fast acting, has low systemic uptake and only results in minor local adverse effects. Furthermore, even though the evidence indicated that ibuprofen foam may significantly reduce chronic leg ulcer pain, it was not considered for this study as it was not on the NSW state contract when the study commenced, therefore, was not on the Central Coast Local Health District formulary which restricted availability. There were no such restrictions for EMLA® and a

published case report (Purcell et al., 2012) indicated the potential usefulness of EMLA ® _{as a}

primary dressing for chronic pain associated with chronic leg ulcers.

The limitations of this review are that publication bias is unclear. Even though a comprehensive search strategy was attended and evaluation of research protocols and interviews with trial investigators may have assisted in assessing study quality more accurately (Soares et al., 2004); this was not carried out. Additionally, it is recommended that at least two researchers screen and appraise the literature to increase the probability of extracting the most relevant articles and

appraising the literature accurately (Bigby & Williams, 2003; Edwards et al., 2002); only one researcher screened and appraised the literature included in this review.